The present invention relates to a continuous process for the enantioselective hydrogenation of alpha ketocarbonyl compounds. In particular, the invention relates to a continuous process for the enantioselective hydrogenation of alpha-ketoesters and alpha-ketolactones.
Orito, et al., U.S. Pat. No. 4,329,487 (xe2x80x9cOrito ""487xe2x80x9d) describes a method for the asymmetric hydrogenation of alpha-ketoesters which includes subjecting an alpha-ketoester to asymmetric hydrogenation in the presence of a platinum-alumina catalyst modified with a solution of a cinchona-alkaloid selected from at least one member of the group of quinine, quinidine, cinchonidine and cinchonine.
According to Orito ""487, alpha-ketoesters are reacted by a batch reaction accomplished in a pressure container such as an autoclave.
The hydrogenation of ketopantolactone over a cinchonidine modified Pt-alumina catalyst in a batch process has been investigated and described by A. Baiker et al. in Journal of Catalysis, 176, 569-571, (1998).
Japanese patent publication JP 62158268 describes the asymmetric hydrogenation of alpha ketolactones in a batch process in the presence of a platinum-carbon catalyst modified with a solution of a cinchona-alkaloid selected from at least one of quinine, cinchonine or cinchonidine. The preparation of the catalyst includes mixing 0.5 g 5% Pt/C with 40 ml 1% cinchonidine/ethanol and refluxing the mixture for 3 hours. The catalyst is separated with a centrifuge. A mixture of the catalyst and e.g. ketopantolactone in benzene is autoclaved to give D-pantolactone. The reaction temperature is about 10 to about 100xc2x0 C. (e.g., room temperature). The hydrogen pressure is normal pressure to about 100 kg/cm2, preferably about 60 kg/cm2.
The drawback of the batch process is the huge reactor volume needed for reaction and solid-liquid separation. Another drawback of the batch process is the need for a stirrer which leads to mechanical abrasion of catalyst particles (M. Garland, H. P. Jalett and H. U. Blaser, Stud. Surf. Sci. Catal. 59 (1991) 177).
It is an object of the present invention to provide a process that overcomes the aforesaid drawbacks, and still preserves the high enantioselectivity characteristic of the batch process.
It has now been found that it is possible to carry out the hydrogenation of alpha-ketocarbonyl compounds continuously.
Thus, the present invention includes a continuous process for catalytic hydrogenation of a substrate containing or consisting of an alpha ketocarbonyl compound which process includes the steps of:
(i) contacting in a reactor a substrate and hydrogen in the presence of a modified platinum catalyst, optionally in the presence of a solvent and, for example, a supercritical co-solvent, at a temperature of from about xe2x88x9220xc2x0 C. to about 100xc2x0 C. and at pressures ranging from about 2 bar to about 150 bar to convert the alpha ketocarbonyl compound to the corresponding alpha hydroxy carbonyl compound;
(ii) continuously feeding the substrate which optionally contains a modifier to the reactor;
(iii) continuously feeding hydrogen to the reactor;
(iv) continuously discharging the reaction product from the reactor; and
(v) recovering the alpha hydroxy carbonyl compound from the reaction product.
Another embodiment of the invention is a process for making alpha hydroxy carbonyl from alpha ketocarbonyl which includes:
(i) continuously feeding a substrate solution and a modified platinum catalyst into an apparatus wherein the substrate solution includes an alpha ketocarbonyl/compound;
(ii) continuously feeding hydrogen into the apparatus;
(iii) continuously discharging a reaction product from the reactor, wherein the temperature in the apparatus is from about xe2x88x9220xc2x0 C. to about 100xc2x0 C. and the pressure in the apparatus is about 2 to about 150 bar.